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UniProtKB - O14493 (CLD4_HUMAN)

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Protein

Claudin-4

Gene

CLDN4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a major role in tight junction-specific obliteration of the intercellular space.By similarity

GO - Molecular functioni

  • identical protein binding Source: UniProtKB
  • structural molecule activity Source: InterPro
  • transmembrane signaling receptor activity Source: ProtInc
Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-HSA-420029. Tight junction interactions.

Protein family/group databases

TCDBi1.H.1.1.6. the claudin tight junction (claudin1) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Claudin-4
Alternative name(s):
Clostridium perfringens enterotoxin receptor
Short name:
CPE-R
Short name:
CPE-receptor
Williams-Beuren syndrome chromosomal region 8 protein
Gene namesi
Name:CLDN4
Synonyms:CPER, CPETR1, WBSCR8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:2046. CLDN4.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 7CytoplasmicSequence analysis7
Transmembranei8 – 28HelicalSequence analysisAdd BLAST21
Topological domaini29 – 81ExtracellularSequence analysisAdd BLAST53
Transmembranei82 – 102HelicalSequence analysisAdd BLAST21
Topological domaini103 – 117CytoplasmicSequence analysisAdd BLAST15
Transmembranei118 – 138HelicalSequence analysisAdd BLAST21
Topological domaini139 – 160ExtracellularSequence analysisAdd BLAST22
Transmembranei161 – 181HelicalSequence analysisAdd BLAST21
Topological domaini182 – 209CytoplasmicSequence analysisAdd BLAST28

GO - Cellular componenti

  • apical plasma membrane Source: Ensembl
  • apicolateral plasma membrane Source: Ensembl
  • basal plasma membrane Source: Ensembl
  • bicellular tight junction Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • lateral plasma membrane Source: Ensembl
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Tight junction

Pathology & Biotechi

Involvement in diseasei

CLDN4 is located in the Williams-Beuren syndrome (WBS) critical region. WBS results from a hemizygous deletion of several genes on chromosome 7q11.23, thought to arise as a consequence of unequal crossing over between highly homologous low-copy repeat sequences flanking the deleted region.

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi208Y → F: Loss of phosphorylation by EPHA2. 1 Publication1

Keywords - Diseasei

Williams-Beuren syndrome

Organism-specific databases

DisGeNETi1364.
OpenTargetsiENSG00000189143.
PharmGKBiPA26572.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001447431 – 209Claudin-4Add BLAST209

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei208Phosphotyrosine; by EPHA21 Publication1

Post-translational modificationi

Phosphorylated. Phosphorylation by EPHA2 is stimulated by EFNA1 and alters interaction with TJP1.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO14493.
PaxDbiO14493.
PeptideAtlasiO14493.
PRIDEiO14493.

PTM databases

iPTMnetiO14493.
PhosphoSitePlusiO14493.

Expressioni

Gene expression databases

BgeeiENSG00000189143.
CleanExiHS_CLDN4.
ExpressionAtlasiO14493. baseline and differential.
GenevisibleiO14493. HS.

Organism-specific databases

HPAiCAB002610.

Interactioni

Subunit structurei

Directly interacts with TJP1/ZO-1 (PubMed:16236711). Interacts with TJP2/ZO-2 and TJP3/ZO-3 (By similarity). Interacts with EPHA2; phosphorylates CLDN4 and may regulate tight junctions (PubMed:16236711). Interacts with CLDN1 (PubMed:20375010).By similarity2 Publications

GO - Molecular functioni

Complete GO annotation...

Protein-protein interaction databases

BioGridi107756. 2 interactors.
IntActiO14493. 3 interactors.

Structurei

Secondary structure

1209
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi1 – 3Combined sources3
Helixi7 – 26Combined sources20
Beta strandi30 – 35Combined sources6
Beta strandi44 – 48Combined sources5
Beta strandi50 – 61Combined sources12
Beta strandi63 – 66Combined sources4
Helixi75 – 96Combined sources22
Turni102 – 106Combined sources5
Helixi117 – 148Combined sources32
Beta strandi154 – 160Combined sources7
Helixi163 – 182Combined sources20

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5B2GX-ray3.50A/C/E/G1-183[»]
ProteinModelPortaliO14493.
SMRiO14493.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 103Interaction with EPHA21 PublicationAdd BLAST103
Regioni208 – 209Interactions with TJP1, TJP2 and TJP3By similarity2

Sequence similaritiesi

Belongs to the claudin family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IIJR. Eukaryota.
ENOG410YA61. LUCA.
GeneTreeiENSGT00760000118928.
HOGENOMiHOG000220937.
HOVERGENiHBG000643.
InParanoidiO14493.
KOiK06087.
OMAiTAHNVIR.
OrthoDBiEOG091G0MMR.
PhylomeDBiO14493.
TreeFamiTF331936.

Family and domain databases

InterProiView protein in InterPro
IPR006187. Claudin.
IPR003550. Claudin4.
IPR017974. Claudin_CS.
IPR004031. PMP22/EMP/MP20/Claudin.
PANTHERiPTHR12002. PTHR12002. 1 hit.
PfamiView protein in Pfam
PF00822. PMP22_Claudin. 1 hit.
PRINTSiPR01379. CLAUDIN4.
PROSITEiView protein in PROSITE
PS01346. CLAUDIN. 1 hit.

Sequencei

Sequence statusi: Complete.

O14493-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASMGLQVMG IALAVLGWLA VMLCCALPMW RVTAFIGSNI VTSQTIWEGL 
        60         70         80         90        100
WMNCVVQSTG QMQCKVYDSL LALPQDLQAA RALVIISIIV AALGVLLSVV 
       110        120        130        140        150
GGKCTNCLED ESAKAKTMIV AGVVFLLAGL MVIVPVSWTA HNIIQDFYNP 
       160        170        180        190        200
LVASGQKREM GASLYVGWAA SGLLLLGGGL LCCNCPPRTD KPYSAKYSAA 

RSAAASNYV
Length:209
Mass (Da):22,077
Last modified:January 1, 1998 - v1
Checksum:i0659A93AA5F0E4C5
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000712 mRNA. Translation: BAA22984.1.
BT006989 mRNA. Translation: AAP35635.1.
BC000671 mRNA. Translation: AAH00671.1.
CCDSiCCDS5560.1.
RefSeqiNP_001296.1. NM_001305.4.
UniGeneiHs.647036.
Hs.729359.

Genome annotation databases

EnsembliENST00000340958; ENSP00000342445; ENSG00000189143.
ENST00000431918; ENSP00000388639; ENSG00000189143.
ENST00000435050; ENSP00000409544; ENSG00000189143.
GeneIDi1364.
KEGGihsa:1364.

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000712 mRNA. Translation: BAA22984.1.
BT006989 mRNA. Translation: AAP35635.1.
BC000671 mRNA. Translation: AAH00671.1.
CCDSiCCDS5560.1.
RefSeqiNP_001296.1. NM_001305.4.
UniGeneiHs.647036.
Hs.729359.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5B2GX-ray3.50A/C/E/G1-183[»]
ProteinModelPortaliO14493.
SMRiO14493.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107756. 2 interactors.
IntActiO14493. 3 interactors.

Protein family/group databases

TCDBi1.H.1.1.6. the claudin tight junction (claudin1) family.

PTM databases

iPTMnetiO14493.
PhosphoSitePlusiO14493.

Proteomic databases

EPDiO14493.
PaxDbiO14493.
PeptideAtlasiO14493.
PRIDEiO14493.

Protocols and materials databases

DNASUi1364.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000340958; ENSP00000342445; ENSG00000189143.
ENST00000431918; ENSP00000388639; ENSG00000189143.
ENST00000435050; ENSP00000409544; ENSG00000189143.
GeneIDi1364.
KEGGihsa:1364.

Organism-specific databases

CTDi1364.
DisGeNETi1364.
GeneCardsiCLDN4.
HGNCiHGNC:2046. CLDN4.
HPAiCAB002610.
MIMi602909. gene.
neXtProtiNX_O14493.
OpenTargetsiENSG00000189143.
PharmGKBiPA26572.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IIJR. Eukaryota.
ENOG410YA61. LUCA.
GeneTreeiENSGT00760000118928.
HOGENOMiHOG000220937.
HOVERGENiHBG000643.
InParanoidiO14493.
KOiK06087.
OMAiTAHNVIR.
OrthoDBiEOG091G0MMR.
PhylomeDBiO14493.
TreeFamiTF331936.

Enzyme and pathway databases

ReactomeiR-HSA-420029. Tight junction interactions.

Miscellaneous databases

ChiTaRSiCLDN4. human.
GeneWikiiCLDN4.
GenomeRNAii1364.
PROiPR:O14493.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000189143.
CleanExiHS_CLDN4.
ExpressionAtlasiO14493. baseline and differential.
GenevisibleiO14493. HS.

Family and domain databases

InterProiView protein in InterPro
IPR006187. Claudin.
IPR003550. Claudin4.
IPR017974. Claudin_CS.
IPR004031. PMP22/EMP/MP20/Claudin.
PANTHERiPTHR12002. PTHR12002. 1 hit.
PfamiView protein in Pfam
PF00822. PMP22_Claudin. 1 hit.
PRINTSiPR01379. CLAUDIN4.
PROSITEiView protein in PROSITE
PS01346. CLAUDIN. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiCLD4_HUMAN
AccessioniPrimary (citable) accession number: O14493
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: June 7, 2017
This is version 146 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.